Patients with Alzheimer's disease have, among other abnormalities, loss of markers for acetylcholine and glutamate. The impaired memory accompanying this disease suggests a critical function for these two neurochemicals in mnemonic processes. In support of this proposal, we have found that visual recognition memory in macaques is impaired following either excitotoxic lesions of the basal forebrain cholinergic system or administration in normal monkeys of the muscarinic receptor antagonist scopolamine and the NMDA-type glutamate receptor antagonist MK-801. In addition, we found that scopolamine affects primary as well as secondary memory, and memory storage, not retrieval. We have shown that the cholinesterase inhibitors physostigmine, THA, and E2020 all produce significant, though small, improvements in performance. Additionally, we have found that D-cycloserine, an agonist at the glycine binding site on the NMDA receptor, produces an even greater improvement in memory than do the cholinesterase inhibitors. Using in vivo microdialysis, we have shown that acetylcholine release is increased in the hippocampus and inferior temporal and perirhinal cortices when an animal is actively performing any task compared to when it is sitting quietly. Using direct intracranial injections, we have found that scopolamine impairs recognition when injected into the perirhinal cortex, but not into the inferior temporal cortex or the dentate gyrus of the hippocampus.